Ginsenoside Rg3 exerts antiproliferation activity on cancer cells by regulating diverse noncoding RNAs. However, little is known about the role of long noncoding RNAs (lncRNAs) or their relationship with competitive endogenous RNA (ceRNA) in Rg3-treated cancer cells. Here, a lncRNA (ATXN8OS) was found to be downregulated via Rg3-mediated promoter hypermethylation in MCF-7 breast cancer cells. SiRNA-induced downregulation of ATXN8OS decreased cell proliferation but increased apoptosis, suggesting that the noncoding RNA possessed proproliferation activity. An in silico search for potential ATXN8OS-targeting microRNAs (miRs) identified a promising candidate (miR-424-5p) based on its high binding score. As expected, miR-424-5p suppressed proliferation and stimulated apoptosis of the MCF-7 cells. The in silico miR-target-gene prediction identified 200 potential target genes of miR-424-5p, which were subsequently narrowed down to seven that underwent hypermethylation at their promoter by Rg3. Among them, three genes (EYA1, DACH1, and CHRM3) were previously known oncogenes and were proven to be oppositely regulated by ATXN8OS and miR-424-5p. When taken together, Rg3 downregulated ATXN8OS that inhibited the tumor-suppressive miR-424-5p, leading to the downregulation of the oncogenic target genes.

中文翻译：

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人参皂苷Rg3防止致癌的长非编码RNA ATXN8OS抑制乳腺癌细胞中的肿瘤抑制性microRNA-424-5p

人参皂苷Rg3通过调节多种非编码RNA在癌细胞上发挥抗增殖活性。然而，人们对Rg3处理的癌细胞中长非编码RNA（lncRNA）的作用或其与竞争性内源RNA（ceRNA）的关系知之甚少。在这里，在MCF-7乳腺癌细胞中，lncRNA（ATXN8OS）通过Rg3介导的启动子高甲基化被下调。SiRNA诱导的ATXN8OS的下调减少了细胞增殖，但增加了细胞凋亡，表明非编码RNA具有增殖活性。在计算机上搜索潜在的靶向ATXN8OS的microRNA（miR），基于其高结合得分，鉴定出了有前途的候选基因（miR-424-5p）。如预期的那样，miR-424-5p抑制了MCF-7细胞的增殖并刺激了其凋亡。在计算机上进行的miR-靶标基因预测可识别出200个可能的miR-424-5p靶标基因，随后将其缩小为7个，在它们的启动子上通过Rg3进行了超甲基化。其中，三个基因（EYA1，DACH1和CHRM3）是先前已知的癌基因，并被证明受ATXN8OS和miR-424-5p的相反调控。放在一起，Rg3下调了抑制肿瘤抑制性miR-424-5p的ATXN8OS，从而导致了致癌靶基因的下调。